Second malignancies in patients with myeloproliferative neoplasms: a population-based cohort study of 9379 patients

Abstract

To determine the risk of a wide range of second malignancies in patients with myeloproliferative neoplasms (MPNs), we conducted a large population-based study and compared the results to matched controls. From national Swedish registers, 9379 patients with MPNs diagnosed between 1973 and 2009, and 35,682 matched controls were identified as well as information on second malignancies, with follow-up until 2010. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were calculated using Cox regression and a flexible parametric model. There was a significantly increased risk of any non-hematologic cancer with HR of 1.6 (95% CI: 1.5-1.7). The HRs for non-melanoma skin cancer was 2.8 (2.4-3.3), kidney cancer 2.8 (2.0-4.0), brain cancer 2.8 (1.9-4.2), endocrine cancers 2.5 (1.6-3.8), malignant melanoma 1.9 (1.4-2.7), pancreas cancer 1.8 (1.2-2.6), lung cancer 1.7 (1.4-2.2), and head and neck cancer 1.7 (1.2-2.6). The HR of second malignancies was similar across all MPN subtypes, sex, and calendar periods of MPN diagnosis. The risk of developing a hematologic malignancy was also significantly increased; the HR for acute myeloid leukemia was 46.0 (32.6-64.9) and for lymphoma 2.6 (2.0-3.3). In conclusion, our study provides robust population-based support of an increased cancer risk in MPN patients.

Second cancers in MPN: Survival analysis from an international study

“…[1][2][3][4][5] Blood and solid cancers occur in about 17% of patients with MPN, often preceding the diagnosis of MPN: melanoma, prostate cancer and non-MPN blood cancers have been diagnosed in excess as compared with control population in North Europe registry studies. In addition to these incident events, recent studies consistently reported that MPN patients are also prone to an increased risk of developing second cancers (SC).…”

Myeloproliferative and lymphoproliferative disorders: State of the art

“…Registry‐based population studies demonstrate that patients with MPN are at increased risk of developing both new hematologic and nonhematologic cancers . Among hematologic neoplasms, the risk is increased mainly for myeloid neoplasms; however, the risk for developing non‐Hodgkin lymphoma is also increased (hazard ratio 2.6) . A systematic review of published literature regarding concurrent MPN and LPN has recently been published .…”

“…Myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are clonal disorders complicated mainly by vascular events and transformation to myelofibrosis (for PV and ET) or leukemia . Secondary malignancies, in particular, lymphoproliferative disorders (LPNs), are rare but occur at a higher frequency than found in the general population …”

B‐cell frequencies and immunoregulatory phenotypes in myeloproliferative neoplasms: Influence of ruxolitinib, interferon‐α2, or combination treatment

“…Furthermore, the effect of ruxolitinib (RUX) or interferon‐α2 (IFN‐α2) treatment on B cells in patients with MPNs is unknown . MPNs arise from somatic mutations, including the Januskinase‐2 (JAK2) ‐V617F mutation, in hematopoietic stem cells, and they are associated with secondary cancers and autoimmune disorders . MPNs are characterized by a state of chronic inflammation in the bone marrow, and chronic inflammation favors myeloid differentiation over lymphoid differentiation .…”

“…Activated B cells also express PD‐1, and an immunoregulatory role of IL‐10‐producing PD‐1 hi B cells has been suggested in hepatocellular carcinoma . It is therefore conceivable that the B‐cell phenotype pattern in patients with MPNs influences the development of immune deregulation and associated complications, including second cancers …”